Patients predisposed or at increased risk of renal dysfunction include those with any degree of preexisting renal insufficiency, diabetes mellitus, age >65 years, volume depletion, sepsis, paraproteinemia, or concomitant therapy with nephrotoxic drugs.125151263265266280282308324325326332

Uses for Immune Globulin

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)

IGIM is used to provide short-term passive immunity to HAV infection for preexposure prophylaxis in certain susceptible individuals at risk of exposure to the virus.105115154186187231336

Primary immunization with an age-appropriate schedule of hepatitis A vaccine is preferred for HAV preexposure prophylaxis in adults, adolescents, children, and infants ≥12 months of age since active immunization provides long-term protection.186187

IGIM can be used alone for HAV preexposure prophylaxis when the vaccine is unavailable or cannot be used (e.g., infants <12 months of age, individuals hypersensitive to vaccine components) or when traveler chooses not to receive the vaccine, provided that only short-term protection is required.105115186187231

Combined passive immunization with IGIM and active immunization with hepatitis A vaccine should be used in those who require both immediate and long-term protection against HAV.105186187195196197198208

Travelers to areas with intermediate or high levels of endemic HAV are at risk of exposure to the disease.115186187

Risk of acquiring HAV while traveling varies with living conditions, length of stay, and incidence of HAV infection in the area visited.115186 Consider that many cases of HAV occur in travelers to developing countries with standard tourist itineraries, accommodations, and food consumption behaviors.115 Consult CDC website ([Web]) for information regarding which countries have high or intermediate levels of HAV endemicity.115

USPHS Advisory Committee on Immunization Practices (ACIP) and CDC recommend preexposure prophylaxis with hepatitis A vaccine and/or IGIM in all susceptible individuals traveling for any purpose, frequency, or duration to areas where risk of exposure to HAV is intermediate or high.115186187 Some experts advise individuals traveling outside the US to consider preexposure prophylaxis with hepatitis A vaccine regardless of their travel destination.115

For optimal protection in travelers at greatest risk for HAV (older adults or individuals with altered immunocompetence, chronic liver disease, or other chronic medical condition) who plan to depart in <2 weeks, ACIP and CDC recommend that a single dose of IGIM be given for preexposure prophylaxis concurrently with the initial dose of hepatitis A vaccine (at a different site).115187

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)

IGIM is used to provide short-term passive immunity for postexposure prophylaxis of HAV in susceptible individuals with recent (within 2 weeks) exposure to the virus.105154186187336

The choice of active immunization with hepatitis A vaccine and/or passive immunization with IGIM should take into account magnitude of risk associated with the exposure and patient characteristics associated with increased risk of more severe manifestations of HAV (e.g., older age, chronic liver disease).105186187

Although IGIM is 80–90% effective in preventing symptomatic HAV infection if administered within 2 weeks of exposure,105186187 there is some evidence that monovalent hepatitis A vaccine administered within 2 weeks of exposure may be as effective as IGIM in healthy individuals 1–40 years of age.105187287 The vaccine also offers certain advantages over IGIM (e.g., induces active immunity and longer protection, more readily available, easier to administer, greater patient acceptance).187287

For HAV postexposure prophylaxis in healthy individuals 12 months through 40 years of age, including travelers, ACIP and AAP prefer use of monovalent hepatitis A vaccine 105187

For HAV postexposure prophylaxis in adults >40 years of age, including travelers, ACIP prefers IGIM since data not available to date regarding efficacy of the vaccine for postexposure prophylaxis in this age group and these individuals are at risk for more severe manifestations of HAV.187 The vaccine can be used if IGIM cannot be obtained.187

In individuals in whom IGIM is preferred for HAV postexposure prophylaxis, give a dose of hepatitis A vaccine concurrently (using different syringes and different injection sites) if the vaccine is indicated for other reasons (e.g., catch-up vaccination, preexposure vaccination in high-risk groups) and is not contraindicated.105187 If a dose of hepatitis A vaccine is used (with or without IGIM) for HAV postexposure prophylaxis, give an additional (booster) dose of the vaccine according to the usually recommended schedule to ensure long-term protection.105186187

If HAV postexposure prophylaxis indicated, administer as soon as possible (within 2 weeks of exposure).105186187 Data not available regarding efficacy of HAV postexposure prophylaxis administered >2 weeks after exposure.187 Routine serologic screening of contacts for markers of HAV infection prior to administration of HAV postexposure prophylaxis not recommended since this would delay prophylaxis.105186

HAV postexposure prophylaxis is indicated in all previously unvaccinated individuals who have had household or sexual (heterosexual or homosexual) contact (within the past 2 weeks) with an individual with serologically confirmed HAV.105186187 Also consider HAV postexposure prophylaxis for individuals exposed (within the past 2 weeks) through other types of ongoing, close personal contact (e.g., regular babysitting).186187

Contacts who have shared illicit drugs (within the past 2 weeks) with an individual with serologically confirmed HAV should receive HAV postexposure prophylaxis.186187

Administer HAV postexposure prophylaxis to all previously unvaccinated staff and attendees of child-care centers or homes if ≥1 case of HAV is recognized in children or employees or if HAV is recognized in ≥2 households of center attendees (within the past 2 weeks).187 In centers that do not provide care to children who wear diapers, HAV postexposure prophylaxis is indicated only in classroom contacts of the index patient.187 If an outbreak occurs (i.e., HAV in ≥3 families), also consider HAV postexposure prophylaxis for members of households that have diapered children attending the center.187

If HAV is diagnosed in a food handler, ACIP recommends HAV postexposure prophylaxis (within 2 weeks) for other food handlers at the same establishment.186187 Because common-source transmission to patrons unlikely, HAV postexposure prophylaxis is not usually indicated for patrons, but may be considered if the food handler directly handled uncooked or cooked food and had diarrhea or poor hygienic practices and if patrons can be identified and given prophylaxis within 2 weeks after exposure.186187 Settings where repeated HAV exposure might have occurred (e.g., institutional cafeterias) warrant stronger consideration of postexposure prophylaxis for patrons.186187

Health-care personnel, including those exposed to sewage, are not considered at increased risk for HAV infection as the result of occupational exposures.186235 Routine use of HAV postexposure prophylaxis not indicated for health-care personnel providing care for patients with HAV.105186187 Nosocomial HAV transmission is rare.186 If epidemiologic investigation indicates HAV transmission occurred among hospital patients and/or hospital staff, ACIP recommends postexposure prophylaxis against HAV only in individuals in close contact with index patients.187

Measles

IGIM and IGIV are used to prevent or modify symptoms of measles (rubeola) in susceptible individuals exposed to the disease <6 days previously.105115133154

Individuals born before 1957 and individuals with documentation of adequate vaccination against measles at ≥12 months of age, laboratory evidence of measles immunity, or laboratory confirmation of prior measles infection have acceptable presumptive evidence of measles immunity.105133 Consider other individuals susceptible to measles.133

Postexposure vaccination (i.e., within 72 hours of exposure) with a vaccine containing measles virus vaccine live (e.g., measles, mumps, and rubella virus vaccine live; MMR) is recommended by ACIP and AAP and is preferred for postexposure prophylaxis against measles in most susceptible individuals ≥12 months of age who are exposed to measles in most settings (e.g., day-care facilities, schools, colleges, health-care facilities), provided the vaccine can be given within 72 hours of the exposure and is not contraindicated.105133

Postexposure prophylaxis with immune globulin (i.e., within 6 days of exposure) is recommended in certain individuals at risk for severe disease and complications from measles who cannot receive the vaccine, including infants <12 months of age, pregnant women without evidence of measles immunity, and severely immunocompromised patients.105133

When immune globulin is recommended for postexposure prophylaxis against measles, ACIP and AAP state use IGIM for such prophylaxis in infants <12 months of age and use IGIV for such prophylaxis in susceptible pregnant women and severely immunocompromised individuals.105133

In severely immunocompromised patients at increased risk for severe measles and complications (e.g., those with severe primary immunodeficiency, bone marrow transplant recipients, patients being treated for acute lymphocytic leukemia, HIV-infected patients with AIDS), ACIP and AAP recommend postexposure prophylaxis with IGIV within 6 days following exposure, regardless of vaccination status.105133

Because passive immunity to measles following administration of IGIM or IGIV is temporary (unless modified or typical measles occurs), initiate immunization with a vaccine containing measles virus vaccine live (e.g., MMR) at least 6 months after IGIM was given or at least 8 months after IGIV was given, providing the individual is ≥12 months of age and there are no contraindications to the vaccine.105133

Do not give the vaccine concurrently with immune globulin.105133134 (See Specific Drugs and Laboratory Tests under Interactions.)

Mumps

IGIM is not effective for and should not be used for postexposure prophylaxis or treatment of mumps infection.133

Poliomyelitis

IGIM is not indicated for and should not be used for postexposure prophylaxis or treatment of poliomyelitis.154

Rubella

IGIM is not indicated for and should not be used for routine prophylaxis or treatment of rubella.105131154

Although there is some evidence that use of IGIM for postexposure prophylaxis in susceptible women exposed to rubella during first trimester of pregnancy may lessen likelihood of rubella infection and associated adverse fetal effects,131154 ACIP and AAP state that use of IGIM after exposure to rubella will not prevent infection or viremia but may modify or suppress symptoms and can create an unwarranted sense of security.105131235 Infants with congenital rubella have been born to women who received IGIM shortly after exposure to the disease.105131235

ACIP and AAP state that IGIM should not be used routinely for postexposure prophylaxis of rubella in early pregnancy or any other circumstance.105131 The only instance in which IGIM might be considered for postexposure prophylaxis of rubella is in a susceptible pregnant woman who is exposed to a confirmed case of rubella early in the pregnancy and who will not consider terminating the pregnancy under any circumstances.105131154 In such cases, administration within 72 hours of exposure might reduce, but will not eliminate, risk for rubella.131

Varicella

IGIV has been used and is recommended as an alternative to varicella-zoster immune globulin (VZIG) for postexposure prophylaxis of varicella† in susceptible individuals when VZIG is unavailable.105156268272

Although manufacturer states that IGIM may be considered an alternative to VZIG for postexposure prophylaxis of varicella in susceptible individuals who are immunocompromised,154 IGIV (not IGIM) is recommended when VZIG is unavailable.105156272

VZIG is the preferred immune globulin for postexposure prophylaxis of varicella in individuals who do not have evidence of immunity (i.e., without a history of varicella or varicella vaccination) and are at high risk for severe disease and complications (e.g., HIV-infected or other immunocompromised individuals, pregnant women).105146155156269272

Clinical data demonstrating effectiveness of IGIV for postexposure prophylaxis not available.105272 Commercially available IGIV preparations contain anti-varicella antibody titers, but the titer of any specific IGIV lot is uncertain since IGIV not routinely tested for anti-varicella antibodies.105272

ACIP, AAP, CDC, NIH, and others state that HIV-infected adults, adolescents, or children or other individuals who are receiving IGIV replacement therapy (≥400 mg/kg given at regular intervals) and received a dose of IGIV within 3 weeks prior to exposure to wild-type varicella zoster virus should be protected and should not require postexposure prophylaxis with VZIG or IGIV.105146155156269

Although VZIG or IGIV given shortly after exposure to varicella zoster virus can prevent or modify the course of the disease, immune globulin preparations not effective once disease established.105

Concomitant use of IGIV and high-dose aspirin therapy initiated within 10 days of the onset of fever is more effective than aspirin alone in preventing or reducing the occurrence of coronary artery abnormalities associated with Kawasaki disease and may result in more rapid resolution of fever and other manifestations of acute inflammation.104105128151280299

AAP, AHA, and American College of Chest Physicians (ACCP) state that combined therapy with IGIV and aspirin should be administered as soon as possible after Kawasaki disease is diagnosed or strongly suspected (optimally within 7–10 days of disease onset).105299300 In those with a delayed diagnosis (i.e., >10 days after disease onset), AAP and AHA suggest initiation of combined therapy with IGIV and aspirin if the patient has unexplained persistent fever or aneurysms and manifestations of ongoing systemic inflammation (elevated erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) or evolving CAD.105299

Approximately ≥10% of patients with Kawasaki disease fail to respond to initial treatment with IGIV and aspirin therapy and have persistent fever or recurrent fever after an initial afebrile period.105299 Retreatment with IGIV (within 24–48 hours of persistent or recrudescent fever) and continued aspirin therapy usually is recommended for these patients.105299

Coronary artery abnormalities develop in 15–25% of children with Kawasaki disease if they are not treated within 10 days of fever onset;105299300 approximately 4% of patients develop coronary artery abnormalities despite prompt treatment with IGIV and aspirin.105 Long-term management of those who develop coronary abnormalities depends on the severity of coronary involvement and may include low-dose aspirin (with or without clopidogrel or dipyridamole), anticoagulant therapy with warfarin or low molecular weight heparin, or a combination of antiplatelet and anticoagulant therapy (usually low-dose aspirin and warfarin).105299300

Chronic Inflammatory Demyelinating Polyneuropathy

IGIV (i.e., Gammaked 10%, Gamunex-C 10%) is used for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse.265298332

Some clinicians consider IGIV the preferred treatment for CIDP, especially in children†, patients with poor venous access that precludes use of plasma exchange, and in those susceptible to complications of long-term corticosteroid therapy.305306

Multifocal Motor Neuropathy

IGIV (i.e., Gammagard Liquid 10%) is used for maintenance treatment to improve muscle strength and disability in adults with multifocal motor neuropathy (MMN).266

Some clinicians recommend IGIV as a treatment of choice for MMN301305306310311 when disability is severe enough to warrant treatment.311

Other Neurologic and Neuromuscular Disorders

IGIV is used in the treatment of Guillain-Barré syndrome† (GBS).165219301304305306310312317318 Although safety and efficacy not established, IGIV initiated within 2 weeks of symptom onset appears to be as effective as plasma exchange218301305306310312317 and is recommended by some clinicians as a treatment of choice for GBS in adults or children,218301305306310312318 especially if disease is severe.301312 Additional study needed to determine whether IGIV is beneficial in patients with mild GBS or Miller Fischer syndrome.310312317

IGIV has been used in the management of multiple sclerosis† (MS).301305306310318 Benefits (e.g., reduced exacerbations, reduced disability scores) reported in some patients with relapsing-remitting MS,301305306310318 but these findings not confirmed with subsequent studies.333334 Although some clinicians suggest that IGIV can be considered as a potentially effective second- or third-line treatment in patients with relapsing-remitting MS,306310 others state IGIV not recommended for treatment of relapsing-remitting333 or secondary progressive MS310333 or treatment of chronic symptoms of MS.310

IGIV has been used with some success in the treatment of myasthenia gravis†108110217301304305306310312318319320 and Lambert-Eaton myasthenic syndrome† (LEMS).301306318320322 Efficacy and safety not established and further study needed.305306318320 Some clinicians suggest IGIV may be beneficial for second-line or adjunctive treatment of severe or worsening myasthenia gravis when other treatments unsuccessful or not tolerated218306318320 and also can be considered for second-line treatment of LEMS.306320322 Although there is some evidence that IGIV may be beneficial in patients with severe myasthenia gravis exacerbation,310312319320 data insufficient regarding use of the drug (either alone or in conjunction with other agents) in those with stable or chronic myasthenia gravis.310312319320

IGIV may provide some benefits in the management of Stiff-person syndrome† (Moersch-Woltmann syndrome).301304305306310312321 Although efficacy and safety not established, some clinicians recommend use of IGIV as second-line treatment when other treatments have been unsuccessful or cannot be used.301310

IGIV has been used in a limited number of children with intractable epilepsy†.218306 There is some evidence that IGIV may be beneficial in some patients with Lennox-Gastaut syndrome† or Rasmussen syndrome†,306310 but further study needed.145157165218 Although efficacy and safety not established, some clinicians suggest IGIV can be considered in children with intractable epilepsy if they have not responded to antiepileptic agents and corticosteroids,306310 especially if they are otherwise candidates for surgical resection.306

Infections in HIV-infected Individuals

IGIV has been used in an attempt to control or prevent infections and improve immunologic parameters in children with symptomatic HIV infection† who are immunosuppressed in association with AIDS or AIDS-related complex (ARC).130139144145156157175176177178179180181184216

IGIV also has been used in an attempt to control or prevent infections in HIV-infected adults†.130144145157

IGIV reduces incidence of recurrent bacterial infections and sepsis, including upper respiratory tract infections, in adults and children with symptomatic HIV infection.144145157175176177178216

ACIP, AAP, CDC, NIH, and other experts state that HIV-infected infants and children with hypogammaglobulinemia (IgG <400 mg/dL) should receive IGIV (400 mg/kg once every 2–4 weeks) to prevent serious bacterial infections.156 These experts state that use of IGIV is no longer recommended for routine primary prophylaxis of serious bacterial infections in HIV-infected infants and children;156 IGIV should be used for such prophylaxis only if hypogammaglobulinemia is present or functional antibody deficiency is demonstrated by either poor specific antibody titers or recurrent bacterial infections.156

Infections in Bone Marrow Transplant (BMT) Recipients

IGIV has been used in adults and children undergoing BMT† to decrease the risk of infections (e.g., septicemia), interstitial pneumonia of infectious or idiopathic etiologies, and acute graft-versus-host disease (GVHD).221223224225306

Effect of IGIV on the incidence of cytomegalovirus (CMV) infection, other infections, or GVHD in patients undergoing allogeneic BMT is unclear.221222223224225304306 IGIV prophylaxis in BMT patients does not appear to affect survival or risk of cancer relapse, and the long-term effects of such therapy remain to be determined.221

Although efficacy and safety in BMT patients not established, some clinicians suggest that IGIV be used for prophylaxis in all allogeneic BMT patients, especially CMV-positive patients or those who have received a transplant from a CMV-positive donor.222

Some clinicians suggest that, although there is a perceived benefit of IGIV prophylaxis in infants with severe combined immunodeficiency or other primary immunodeficiency diseases undergoing BMT, the effect of IGIV in these children is difficult to study since they generally are receiving IGIV for replacement therapy.306 These clinicians also state that use of IGIV appears to offer little benefit in patients with malignancies undergoing HLA-identical sibling BMT and that additional study is needed to determine whether the drug is beneficial in those undergoing HLA-matched unrelated BMT or cord blood transplants.306

Infections in Hematopoietic Stem Cell Transplant (HSCT) Recipients

CDC, IDSA, and American Society of Blood and Marrow Transplantation (ASBMT) state that, although routine use of IGIV for prophylaxis is not recommended for autologous HSCT recipients, some clinicians recommend use of IGIV to prevent bacterial infections (e.g., Streptococcus pneumoniae sinopulmonary infections) in adult, adolescent, or pediatric allogeneic HSCT recipients† who experience severe hypogammaglobulinemia (IgG <400 mg/dL) within the first 100 days after transplant.262

Routine administration of IGIV in HSCT recipients >90 days after HSCT is not recommended in the absence of severe hypogammaglobulinemia.262

Infections in Low-birthweight Neonates

IGIV has been used for prophylaxis and treatment of infections in certain high-risk, preterm, low-birthweight neonates†.130137144145157166167168169170171172214 However, use of IGIV for prophylaxis of infections in high-risk neonates is controversial.144145157167170183214 AAP does not recommend routine use of IGIV for prophylaxis of infections in preterm neonates.105

Autoimmune Neutropenia and Autoimmune Hemolytic Anemia

IGIV has been used with some success in a limited number of adults and children for the treatment of autoimmune neutropenia†.130138140145157164 May be beneficial in some patients,304306 but unclear whether IGIV offers any advantage over corticosteroid therapy.306

IGIV has been used with variable results in patients with autoimmune hemolytic anemia†.130140142143157 Some clinicians state IGIV should be used in the management of autoimmune hemolytic anemia only in those who fail to respond to other treatment options.306

Dermatomyositis and Polymyositis

IGIV has resulted in improvements (e.g., in muscle strength, neuromuscular symptoms, rash, scaling) in a limited number of patients with biopsy-proven, treatment-resistant dermatomyositis.220 Although efficacy and safety not established, it has been suggested that IGIV (usually in conjunction with corticosteroids) may be beneficial as second-line therapy in patients with dermatomyositis when other therapies are unsuccessful or cannot be used.218301305306310312318

Graves’ Ophthalmopathy

IGIV has been used with some success in the management of Graves’ ophthalmopathy†.301302303304305306

Some patients responded to IGIV with improvements in diplopia, proptosis, visual acuity, and intraocular pressure;302303 response rate appeared similar to that obtained with corticosteroid treatment.301302303305

Systemic Lupus Erythematosus

IGIV has been used with some success in the treatment of systemic lupus erythematosus† (SLE);218301304305306 efficacy and safety not definitely established and additional study needed.305306

Some clinicians suggest use of IGIV may be considered in patients with severe active SLE when other drugs have been ineffective or not tolerated;218 other clinicians recommend caution.306

Tetanus

IGIV has been recommended as an alternative for the treatment of tetanus† when tetanus immune globulin (TIG) is unavailable;105 TIG is the immune globulin of choice.105

IGIV has been recommended as an alternative for postexposure prophylaxis of tetanus† in individuals with tetanus-prone wounds when TIG is unavailable;105 TIG is the immune globulin of choice.105

Toxic Shock Syndrome

IGIV has been used as an adjunct to anti-infectives and surgical intervention in the treatment of staphylococcal or streptococcal toxic shock syndrome† or necrotizing fasciitis† in severely ill patients.105201306323

Although data are limited and efficacy and safety not established, AAP and others suggest use of IGIV may be considered as an adjunct in the management of severe staphylococcal or streptococcal toxic shock syndrome† or necrotizing fasciitis† (e.g., when the infection is refractory to several hours of aggressive therapy, an undrainable focus is present, or the patient has persistent oliguria with pulmonary edema).105323 IGIV most likely to be beneficial if initiated early in the course of the disease.105

In general, in patients receiving initial doses of IGIV or switching from one IGIV preparation to another, initiate IGIV using infusion rate at lower end of recommended range and slowly increase to maximum recommended rate only after patient has tolerated several infusions at an intermediate infusion rate.151266280324325326

If adverse reactions occur during the IGIV infusion, decrease IV infusion rate or stop the infusion until reactions subside.151263265266292308324325326

Rate of Administration

Treatment of primary immunodeficiency: Initiate IV infusion of Bivigam 10% at a rate of 0.5 mg/kg per minute (0.005 mL/kg per minute) for first 10 minutes.324 If tolerated, rate may be gradually increased every 20 minutes by 0.8 mg/kg per minute to a maximum of 6 mg/kg per minute.324 If adverse effects related to IV infusion rate occur, symptoms may disappear if infusion is stopped or slowed.324 If symptoms subside promptly, IV infusion may be resumed at a lower rate that is comfortable for the patient.324

Patients at risk for renal dysfunction or thrombosis (including those ≥65 years of age): Use minimum IV infusion rate practicable.324 Consider discontinuing if renal function deteriorates.324

Manufacturer states that, although the drug may be filtered, filtering not required.125 If filter is used, those with pore sizes of ≥15 μm are less likely to slow the IV infusion, especially when higher concentrations given;125 antimicrobial filters (0.2 μm) may be used.125

After diluent added, swirl vial vigorously to dissolve the drug;125 to avoid foaming, do not shake.125 Generally dissolves within a few minutes, but may take up to 20 minutes for complete dissolution.125

If large doses are to be administered, contents of several reconstituted vials of identical concentration and diluent may be pooled into an empty sterile glass or plastic IV infusion container using aseptic technique.125

Rate of Administration

Treatment of primary immunodeficiency in individuals with previously untreated agammaglobulinemia or hypogammaglobulinemia: Administer initial dose of Carimune NF as a 3% solution (30 mg/mL) at an initial IV infusion rate of 0.5 mg/kg per minute.125 After 30 minutes, infusion rate may be increased to 1 mg/kg per minute for the next 30 minutes; thereafter, infusion rate may be gradually increased in a stepwise manner up to a maximum of 3 mg/kg per minute as tolerated.125 If initial IV infusion well tolerated, higher concentrations may be used for subsequent infusions.125 (See Table 1.) Inflammatory reactions have occurred when initial IV infusion rate >2 mg/kg per minute was used in patients with agammaglobulinemia or hypogammaglobulinemia who had not previously received IGIV or had not received a dose within the last 8 weeks.125 (See Infusion Reactions under Cautions.)

Treatment of ITP: Administer initial dose of Carimune NF as a 6% solution (60 mg/mL) at an initial IV infusion rate of 0.5 mg/kg per minute.125 After 30 minutes, infusion rate may be increased to 1 mg/kg per minute for the next 30 minutes; thereafter, infusion rate may be gradually increased in a stepwise manner up to a maximum of 3 mg/kg per minute as tolerated.125 (See Table 1.)

Rate of Administration

Treatment of primary immunodeficiency: Administer Flebogamma 5% DIF at an initial IV infusion rate of 0.01 mL/kg per minute (0.5 mg/kg per minute).282 If tolerated for first 30 minutes, gradually increase to a maximum infusion rate of 0.1 mL/kg per minute (5 mg/kg per minute).282

Patients ≥65 years of age or at increased risk for renal dysfunction or thrombosis: Use minimum infusion rate practicable.282 Maximum IV infusion rate in geriatric patients is <0.06 mL/kg per minute (<3 mg/kg per minute).282

Rate of Administration

Treatment of primary immunodeficiency: Administer Flebogamma 10% DIF at an initial IV infusion rate of 0.01 mL/kg per minute (1 mg/kg per minute) for 30 minutes;325 if tolerated, IV infusion rate may be increased gradually to 0.04 mL/kg per minute (4 mg/kg per minute).325 If tolerated, may gradually increase to a maximum rate of 0.08 mL/kg per minute (8 mg/kg per minute).325

Treatment of ITP: Administer Flebogamma 10% DIF at an initial IV infusion rate of 0.01 mL/kg per minute (1 mg/kg per minute) for 30 minutes;325 if tolerated, IV infusion rate may be increased gradually to 0.04 mL/kg per minute (4 mg/kg per minute).325 If tolerated, may gradually increase to a maximum rate of 0.08 mL/kg per minute (8 mg/kg per minute).325

Patients ≥65 years of age or at risk for renal dysfunction or thrombosis: Use minimum infusion rate practicable.325 Maximum IV infusion rate in geriatric patients is <0.04 mL/kg per minute (<4 mg/kg per minute).325

Dilution

Available as a 10% solution.266 If necessary, may be diluted with 5% dextrose injection;266 do not use 0.9% sodium chloride as diluent.266 For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Treatment of primary humoral immunodeficiency: Administer Gammagard Liquid 10% at an initial IV infusion rate of 0.5 mL/kg per hour (0.8 mg/kg per minute) for 30 minutes.266 Rate may be increased every 30 minutes (if tolerated) up to a maximum of 5 mL/kg per hour (8 mg/kg per minute).266

Maintenance treatment of MMN: Administer Gammagard Liquid 10% at an initial IV infusion rate of 0.5 mL/kg per hour (0.8 mg/kg per minute).266 Rate may be increased (if tolerated) up to a maximum of 5.4 mL/kg per hour (9 mg/kg per minute).266

Patients >65 years of age or at risk for renal dysfunction or thrombosis: Use minimum IV infusion rate practicable.266 Maximum infusion rate in such patients is <2 mL/kg per hour (<3.3 mg/kg per minute).266

Reconstitution

Reconstitute Gammagard S/D according to the manufacturer’s directions with the sterile water for injection diluent and transfer device provided to prepare a solution containing 50 or 100 mg of protein per mL (5 or 10% solution, respectively).151280

Prior to reconstitution, warm the powder for injection and diluent to room temperature.151280

After diluent added, gently rotate vial to dissolve the drug;151280 to avoid foaming, do not shake.151280

When large doses are to be administered, contents of several vials may be pooled into an empty sterile IV infusion container using aseptic technique.151280

If reconstituted outside of sterile laminar airflow conditions, administer within 2 hours after reconstitution (preferably as soon as possible).151280 If reconstituted in a sterile laminar flow hood using aseptic technique and reconstituted solution stored under constant refrigeration (2–8° C), administer within 24 hours after reconstitution (preferably as soon as possible).151280

Rate of Administration

Administer Gammagard S/D initially as a 5% solution at an initial IV infusion rate of 0.5 mL/kg per hour;151280 if tolerated, gradually increase IV infusion rate of 5% solution to a maximum of 4 mL/kg per hour.151280 If further tolerated, may administer subsequent doses as a 10% solution given initially at an IV infusion rate of 0.5 mL/kg per hour;151280 if tolerated, gradually increase IV infusion rate of 10% solution to a maximum of 8 mL/kg per hour.151280

Patients at increased risk for renal dysfunction or thrombosis: Use minimum rate practicable.151280 Manufacturer recommends maximum IV infusion rate of <3.3 mg/kg per minute (<4 mL/kg per hour as a 5% solution or <2 mL/kg per hour as a 10% solution).151280 However, data are not available to date to identify maximum safe concentration or IV infusion rate in patients at risk for renal dysfunction.151280

IV Administration of Gammaked 10%

Administer Gammaked 10% by IV infusion.332 Alternatively, may be administered by sub-Q infusion for primary immunodeficiency (see Sub-Q Administration of Gammaked 10% under Dosage and Administration).332

Prior to administration, allow to come to room temperature (may take ≥60 minutes);332 should be clear to opalescent and colorless to pale yellow.332

Penetrate the stopper of the 10-mL vial (containing 1 g of protein) with an 18-gauge needle;332 when 25-, 50-, 100-, or 200-mL vials (containing 2.5, 5, 10, or 20 g of protein, respectively) are used, use only 16-gauge needles or dispensing pins to penetrate the vial stopper.332 Promptly use any vial that has been entered;332 discard any partially used vials.332

Contents of full vials may be pooled under aseptic conditions into empty sterile IV infusion bags and infused within 8 hours after pooling.332

Infusion line can be flushed with either 0.9% sodium chloride injection or 5% dextrose injection.332 Do not flush infusion line with heparin because of potential for incompatibility between Gammaked 10% and heparin.332

Dilution

Available as a 10% solution.332 If necessary, may be diluted with 5% dextrose injection;332 do not use saline solutions as diluent.332 For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Primary immunodeficiency diseases or ITP: Administer Gammaked 10% at an initial IV infusion rate of 1 mg/kg per minute (0.01 mL/kg per minute) for first 30 minutes.332 If well tolerated, may gradually increase rate to a maximum IV infusion rate of 8 mg/kg per minute (0.08 mL/kg per minute).332 If adverse effects related to rate of infusion occur, symptoms may disappear if infusion is stopped or slowed.332

Treatment of CIDP: Administer at an initial IV infusion rate of 2 mg/kg per minute (0.02 mL/kg per minute) for first 30 minutes.332 If well tolerated, may gradually increase rate to a maximum IV infusion rate of 8 mg/kg per minute (0.08 mL/kg per minute).332 If adverse effects related to rate of infusion occur, symptoms may disappear if infusion is stopped or slowed.332

Rate of Administration

Primary immunodeficiency or ITP: Administer Gammaplex 5% at an initial IV infusion rate of 0.5 mg/kg per minute (0.01 mL/kg per minute).308 If well tolerated for first 15 minutes, rate may be gradually increased every 15 minutes to a maximum of 4 mg/kg per minute (0.08 mL/kg per minute).308

Penetrate the stopper of the 10-mL vial (containing 1 g of protein) with an 18-gauge needle;265 when 25-, 50-, 100-, 200, or 400-mL vials (containing 2.5, 5, 10, 20, or 40 g of protein, respectively) are used, use only 16-gauge needles or dispensing pins to penetrate the vial stopper.265 Promptly use any vial that has been entered;265 discard any partially used vials.265

Contents of full vials may be pooled under aseptic conditions into empty sterile IV infusion bags and infused within 8 hours after pooling.265

Infusion line can be flushed with either 0.9% sodium chloride injection or 5% dextrose injection.265 Do not flush infusion line with heparin because of potential for incompatibility between Gamunex-C 10% and heparin.265

Dilution

Available as a 10% solution.265 If necessary, may dilute with 5% dextrose injection;265 do not use saline solutions as diluent.265 For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Primary immunodeficiency diseases or ITP: Administer Gamunex-C 10% at an initial IV infusion rate of 1 mg/kg per minute (0.01 mL/kg per minute) for first 30 minutes.265 If well tolerated, may gradually increase rate to a maximum IV infusion rate of 8 mg/kg per minute (0.08 mL/kg per minute).265 If adverse effects related to rate of infusion occur, symptoms may disappear if infusion is stopped or slowed.265

CIDP: Administer at an initial IV infusion rate of 2 mg/kg per minute (0.02 mL/kg per minute) for first 30 minutes.265 If well tolerated, may gradually increase rate to a maximum IV infusion rate of 8 mg/kg per minute (0.08 mL/kg per minute).265 If adverse effects related to rate of infusion occur, symptoms may disappear if infusion is stopped or slowed.265

IV Administration of Octagam 5%

Penetrate the stopper of the single-use bottle with a 16-gauge or smaller needle;263 insert needle only once.263 Promptly use any single-use bottle that has been entered;263 discard partially used bottles.263

If necessary, contents of several single-use bottles may be pooled using aseptic technique;263 infuse within 8 hours after pooling.263

An infusion set is not provided with Octagam 5%;263 if an in-line filter is used (not mandatory), filter pore size should be 0.2–200 μm.263

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection before and after administration of Octagam 5%.263

Rate of Administration

Primary immunodeficiency: Administer Octagam 5% at an initial IV infusion rate of 30 mg/kg per hour (0.5 mg/kg per minute or 0.01 mL/kg per minute) for first 30 minutes.263 If tolerated, increase to 60 mg/kg per hour (1 mg/kg per minute or 0.02 mL/kg per minute) for second 30 minutes and, if further tolerated, to 120 mg/kg per hour (2 mg/kg per minute or 0.04 mL/kg per minute) for third 30 minutes.263 Thereafter, maintain at an IV infusion rate up to a maximum of 200 mg/kg per hour (maximum 3.33 mg/kg per minute or 0.07 mL/kg per minute).263

IV Administration of Octagam 10%

Penetrate the stopper of the single-use bottle with a 16-gauge or smaller needle;326 insert needle only once.326 Promptly use any single-use bottle that has been entered;326 discard partially used bottles.326

If necessary, contents of several single-use bottles may be pooled using aseptic technique;326 infuse within 8 hours after pooling.326

An infusion set is not provided with Octagam 10%;326 if an in-line filter is used (not mandatory), filter pore size should be 0.2–200 μm.326

IV infusion line may be flushed with either 0.9% sodium chloride injection or 5% dextrose injection before and after administration of Octagam 10%.326

Rate of Administration

ITP: Administer Octagam 10% at an initial IV infusion rate of 60 mg/kg per hour (1 mg/kg per minute or 0.01 mL/kg per minute) for first 30 minutes.326 If tolerated, increase to 120 mg/kg per hour (2 mg/kg per minute or 0.02 mL/kg per minute) for second 30 minutes and, if further tolerated, to 240 mg/kg per hour (4 mg/kg per minute or 0.04 mL/kg per minute) for third 30 minutes, and if further tolerated, to 480 mg/kg per hour (8 mg/kg per minute or 0.08 mL/kg per minute).326 Maximum IV infusion rate is 720 mg/kg per hour (maximum 12 mg/kg per minute or 0.12 mL/kg per minute).326

Dilution

Available as 10% solution.292 If necessary, may be diluted with 5% dextrose injection.292 For solution compatibility information, see Compatibility under Stability.

Rate of Administration

Primary immunodeficiency: Administer Privigen 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute).292 If tolerated, rate may be gradually increased to a maximum of 8 mg/kg per minute (0.08 mL/kg per minute).292

Chronic ITP: Administer Privigen 10% at an initial IV infusion rate of 0.5 mg/kg per minute (0.005 mL/kg per minute).292 If tolerated, rate may be gradually increased to a maximum of 4 mg/kg per minute (0.04 mL/kg per minute).292

Patients who have not previously received Privigen 10% (or another immune globulin preparation), patients who have not received the drug within the past 8 weeks, and patients switching from another immune globulin preparation to Privigen 10%: May be at risk of developing inflammatory reactions if rapid IV infusion rate (e.g., >4 mg/kg per minute [>0.04 mL/kg per minute]) used.292 Initiate Privigen10% in such patients using a slow IV infusion rate (e.g., ≤0.5 mg/kg per minute [≤0.005 mL/kg per minute]) and increase rate gradually to maximum rate tolerated.292

Dose may be divided and infused simultaneously in up to 4 different sites that are ≥4 inches apart;331 use of a multi-needle administration set facilitates simultaneous sub-Q infusion at multiple sites.331 Number of sites depends on volume of the dose;331 calculate by dividing total volume to be infused by maximum volume per site.331 For first 2 sub-Q infusions, maximum volume per site is 20 mL in those weighing <40 kg or 60 mL in those weighing ≥40 kg;331 maximum volume per site for subsequent infusions is 60 mL regardless of weight.331

Rate of Administration

Primary immunodeficiency: Administer first 2 sub-Q infusions of Cuvitru 20% at an infusion rate of 10–20 mL/hour at each infusion site.331 For subsequent sub-Q infusions, may increase infusion rate as tolerated to a maximum of 60 mL/hour at each infusion site.331

Sub-Q Administration of Gammagard Liquid 10%

Gammagard Liquid 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency.266 Also may be administered by IV infusion (see IV Administration of Gammagard Liquid 10% under Dosage and Administration).266

May be self-administered sub-Q in the home or other appropriate setting;266 provide patient and/or their caregiver with instructions and training regarding sub-Q administration.266

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lower back using an infusion pump; avoid bony prominences.266

To determine number of infusion sites needed for Gammagard Liquid 10%, divide weekly dose (in mL) by 30 or 20 (i.e., divide by recommended volume per site based on patient weight).266 Sites should be located ≥2 inches apart and should be changed for each weekly dose.266 Use a maximum of 8 simultaneous infusion sites.266

Rate of Administration

Primary immunodeficiency in patients weighing ≥40 kg: For initial sub-Q infusion of Gammagard Liquid 10%, use a volume of 30 mL per site and an infusion rate of 20 mL/hour per site.266 For maintenance doses, use a volume of 30 mL per site and an infusion rate of 20–30 mL/hour per site.266

Primary immunodeficiency in patients weighing <40 kg: For initial sub-Q infusion of Gammagard Liquid 10%, use a volume of 20 mL per site and an infusion rate of 15 mL/hour per site.266 For maintenance doses, use a volume of 20 mL per site and an infusion rate of 15–20 mL/hour per site.266

Sub-Q Administration of Gammaked 10%

Gammaked 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency.332 Also may be administered by IV infusion (see IV Administration of Gammaked 10% under Dosage and Administration).332

May be self-administered sub-Q in the home or other appropriate setting;332 provide patient and/or their caregiver with instructions and training regarding sub-Q administration.332

Prior to administration, allow to come to room temperature (may take ≥60 minutes);332 should be clear to opalescent and colorless to pale yellow.332

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hip using an infusion pump.332

Depending on total volume required, each dose of Gammaked 10% may be divided and infused into multiple sites.332 Use a maximum of 8 simultaneous administration sites in adults (4 infusion sites used simultaneously in most adults);332 use a maximum of 6 simultaneous administration sites in children.332 Infusion sites should be located ≥2 inches apart.332

Rate of Administration

Primary immunodeficiency in adults: Administer Gammaked 10% sub-Q at an infusion rate of 20 mL/hour at each infusion site.332

Primary immunodeficiency in pediatric patients ≥2 years of age weighing ≥25 kg: Administer Gammaked 10% sub-Q at an initial infusion rate of 15 mL/hour at each infusion site.332 Infusion rate may then be increased to 20 mL/hour.332

Primary immunodeficiency in pediatric patients ≥2 years of age weighing <25 kg: Administer Gammaked 10% sub-Q at an infusion rate of 10 mL/hour at each infusion site.332

Sub-Q Administration of Gamunex-C 10%

Gamunex-C 10% may be administered by sub-Q infusion for treatment of primary immunodeficiency.265 Also may be administered by IV infusion (see IV Administration of Gamunex-C 10% under Dosage and Administration).265

May be self-administered sub-Q in the home or other appropriate setting;265 provide patient and/or their caregiver with instructions and training regarding sub-Q administration.265

Should be clear or slightly opalescent and at room temperature (up to 25°C) prior to administration.265

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hip using an infusion pump.265

Depending on total volume required, each dose of Gamunex-C 10% may be divided and infused into multiple sites.265 Use a maximum of 8 simultaneous administration sites in adults (4 infusion sites used simultaneously in most adults);265 use a maximum of 6 simultaneous administration sites in children.265 Infusion sites should be located ≥2 inches apart.265

Rate of Administration

Primary immunodeficiency in adults: Administer Gamunex-C 10% sub-Q at an infusion rate of 20 mL/hour at each infusion site.265

Primary immunodeficiency in pediatric patients ≥2 years of age weighing ≥25 kg: Administer Gamunex-C 10% sub-Q at an initial infusion rate of 15 mL/hour at each infusion site.265 Infusion rate may then be increased to 20 mL/hour.265

Primary immunodeficiency in pediatric patients ≥2 years of age weighing <25 kg: Administer Gamunex-C 10% sub-Q at an infusion rate of 10 mL/hour at each infusion site.265

Sub-Q Administration of Hizentra 20%

May be self-administered in the home or other appropriate setting;294 provide patient and/or their caregiver with instructions and training regarding sub-Q administration.294

Make sub-Q infusions into the abdomen, thighs, upper arms, and/or lateral hips using an infusion pump.294

Depending on total volume required, each dose may be divided and infused into multiple infusion sites.294 Use a maximum of 4 simultaneous administration sites;294 if more sites needed for the full dose, use a maximum of 12 sites consecutively for each infusion.294 Sites should be located ≥2 inches apart and should be changed for each weekly dose.294

Rate of Administration

Primary immunodeficiency: For initial sub-Q infusion of Hizentra 20%, use a maximum volume of 15 mL and a maximum infusion rate of 15 mL/hour at each administration site.294 For subsequent infusions, infusion rate may be increased to a maximum of 25 mL/hour per site as tolerated;294 maximum flow rate should not exceed a total of 50 mL/hour for all sites combined at any time.294 After the fourth infusion, volume at each infusion site may be increased to 20 mL and then increased to a maximum volume of 25 mL per site as tolerated.294

Hyqvia is commercially available as a kit containing a vial of immune globulin subcutaneous 10% copackaged with a vial of recombinant human hyaluronidase.327 Administer both components only by sub-Q infusion sequentially at same infusion site.327

For each dose of Hyqvia, administer entire contents of vial containing recombinant human hyaluronidase component (acts locally to temporarily increase permeability of sub-Q tissue to increase dispersion and absorption of the immune globulin component) first.327 Within approximately 10 minutes after completion of sub-Q infusion of recombinant human hyaluronidase component, administer appropriate dose of the immune globulin subcutaneous 10% component using same sub-Q infusion site and same needle set.327

Do not mix recombinant human hyaluronidase component and immune globulin subcutaneous 10% component together in same container;327 do not mix or administer the individual components with other drugs or infusion fluids.327

May be self-administered in the home or other appropriate setting;327 provide patient and/or their caregiver with instructions and training regarding sub-Q administration.327

Make sub-Q infusions into the abdomen or thighs using an infusion pump.327 Avoid bony prominences or scarred, infected, or inflamed areas.327

In patients weighing ≥40 kg, maximum volume at each sub-Q infusion site is 600 mL.327 In patients weighing <40 kg, maximum volume at each site is 300 mL.327

Depending on total volume required and tolerability, each dose of immune globulin subcutaneous 10% may be divided and administered using 2 infusion sites on opposite sides of the body.327 When 2 sites are used, also divide the dose of recombinant human hyaluronidase and administer half at each site.327

Rotate administration sites on opposite sides of the body between successive infusions.327

Rate of Administration

Recombinant human hyaluronidase component of Hyqvia : Administer sub-Q at an infusion rate of 1–2 mL/minute or as tolerated.327

Immune globulin subcutaneous 10% component of Hyqvia : Administer first 4 or 5 sub-Q infusions using increasing infusion rate and a variable infusion rate (ramp-up period).327 Adjust time intervals and number of rate changes if full dose and maximum rate are tolerated.327

Consult manufacturer’s instructions provided with Hyqvia for specific information on recommended sub-Q infusion rates and time intervals during the ramp-up period.327

Dosage

Pediatric Patients

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)

Travelers to Areas with Intermediate or High Levels of Endemic HAV

IM

Children†: Single dose of 0.1 or 0.2 mL/kg of IGIM in those staying in such areas for up to 1 or 2 months, respectively.154336 If period of exposure in such areas will be ≥2 months, give 0.2 mL/kg once every 2 months.154336

Primary immunization with the age-appropriate schedule of hepatitis A vaccine before an expected exposure to HAV ensures highest level of protection.186187

To ensure protection in travelers who are immunocompromised or have chronic liver disease or other chronic medical conditions and plan to depart within 2 weeks, give single dose of IGIM simultaneously with initial dose of hepatitis A vaccine (using different syringes and different injection sites).115187

The above IGIM dosage is higher than previously recommended.336 This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).336

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)

IM

Infants <12 months of age†, immunocompromised individuals, individuals with chronic liver disease, and whenever hepatitis A vaccine is contraindicated: Give single dose of 0.1 mL/kg of IGIM154336 as soon as possible after exposure (ideally within 2 weeks).105115186187 Data not available regarding efficacy for HAV postexposure prophylaxis if given >2 weeks after exposure.154186187

In individuals receiving IGIM for HAV postexposure prophylaxis and in whom hepatitis A vaccine also recommended for other reasons, give single dose of IGIM concurrently with first dose of hepatitis A vaccine (using different syringes and different injection sites).186187194

Individuals who have received at least 1 dose of hepatitis A vaccine given at least 1 month prior to the current HAV exposure do not need postexposure prophylaxis with IGIM.186

The above IGIM dosage is higher than previously recommended.336 This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).336

Measles

Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.25 mL/kg of IGIM given within 6 days after exposure in susceptible individuals.154 If susceptible child is immunocompromised, manufacturer recommends single dose of 0.5 mL/kg (up to 15 mL) given immediately after the exposure.154

ACIP and AAP recommend single dose of 0.5 mL/kg (up to 15 mL) of IGIM given within 6 days after exposure.105133 ACIP states optimal dose needed to provide protection against measles unknown.133

Individuals currently receiving immune globulin therapy who received IGIV (≥400 mg/kg) within 3 weeks prior to measles exposure or received immune globulin subcutaneous (≥200 mg/kg) for 2 consecutive weeks prior to measles exposure should be sufficiently protected and do not need IGIM for postexposure prophylaxis.105133

IV

Gammaked 10% (children ≥2 years of age): If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to expected measles exposure.332 If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.332

Gamunex-C 10% (children ≥2 years of age): If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to measles exposure.265 If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.265

Octagam 5%: If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area, measles outbreak in US), increase dosage to at least 400 mg/kg just prior to measles exposure.263 If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg as soon as possible after the exposure.263

Sub-Q

Hizentra 20% (children ≥2 years of age): Use minimum total weekly dose of 200 mg/kg for 2 consecutive weeks in those at risk of measles exposure (e.g., susceptible traveler to measles endemic area, measles outbreak in US).294 If a biweekly regimen is being used, give a single dose of at least 400 mg/kg.294 If a susceptible individual has been exposed to measles, give a dose of at least 400 mg/kg as soon as possible after the exposure.294

Varicella

Alternative to VZIG for Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.6–1.2 mL/kg of IGIM;154 use lower range of dosage in those at risk of thrombosis.154

Single dose of 400 mg/kg of IGIV (ideally within 96 hours after exposure).105156272 Consider IGIV only when VZIG is unavailable.272

May not be necessary in patients already receiving immune globulin replacement therapy with IGIV (≥400 mg/kg given at regular intervals) if the last dose was administered within 3 weeks prior to exposure.105146155156269

Gammaplex 5% (children ≥2 years of age): 300–800 mg/kg (6–16 mL/kg) IV once every 3–4 weeks.308 Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.308 If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.308

Privigen 10% (children ≥3 years of age): 200–800 mg/kg (2–8 mL/kg) IV once every 3 to 4 weeks.292 Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.292 If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.292

Sub-Q

Cuvitru 20% (children ≥2 years of age): Give at regular intervals ranging from once daily up to once every 2 weeks (biweekly).331 Calculate initial sub-Q dose based on monthly dose of prior immune globulin regimen.331 If switching from IGIV or immune globulin subcutaneous 10% with recombinant human hyaluronidase (Hyqvia), give initial dose 1 week after last dose of the other immune globulin.331Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.331

Gammaked 10% (children ≥2 years of age): Administer sub-Q once weekly.332 Give initial dose 1 week after last IGIV dose.332 To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether the patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37.332 Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response.332Consult manufacturer’s literature for specific information on how to adjust sub-Q dosage based on trough serum IgG concentrations and for information regarding dosage requirements for patients switching from another immune globulin subcutaneous preparation to Gammaked 10%.332

Gamunex-C 10% (children ≥2 years of age): Administer sub-Q once weekly.265 Give initial dose 1 week after last IGIV dose.265 To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether the patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37.265 Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response.265Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.265

Hizentra 20% (children ≥2 years of age): Administer sub-Q at regular intervals ranging from once daily up to once every 2 weeks (biweekly).294 Use only in patients who have been receiving IGIV for ≥3 months before being switched to Hizentra 20%;294 give initial dose 1 week after last IGIV dose.294Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.294

Idiopathic Thrombocytopenic Purpura (ITP)

IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg IV once daily for 2–5 consecutive days.125 For treatment of acute childhood ITP, if an initial platelet count response to first 2 doses is adequate (30,000–50,000/mm3), discontinue therapy after second day of the 5-day regimen.125 For treatment of chronic ITP, if platelet count decreases to <30,000/mm3 and/or clinically important bleeding becomes apparent following initial induction therapy, administer 400 mg/kg as a single maintenance infusion.125 If adequate response does not occur, increase maintenance dose to 800–1000 mg/kg given as a single infusion.125

Flebogamma 10% DIF (children ≥2 years of age): 1 g/kg IV once daily for 2 consecutive days for chronic ITP.325

Kawasaki Disease

IV

For initial treatment of acute phase, AHA, AAP, and ACCP recommend a single dose of 2 g/kg of IGIV given in conjunction with aspirin (80–100 mg/kg daily for up to 14 days, then 1–5 mg/kg once daily for 6–8 weeks); initiate as soon as possible (optimally within 7–10 days of disease onset).105299300 If there is no response (i.e., fever persists or recurs ≥36 hours after initial IGIV dose), retreatment with another single dose of 2 g/kg of IGIV (given within 24–48 hours of persistent or recrudescent fever) and continued aspirin therapy is recommended.105299

Gammagard S/D or Gammagard S/D (IgA <1 mcg/mL): Manufacturer recommends a single dose of 1 g/kg IV beginning within 7 days of onset of fever or, alternatively, 400 mg/kg once daily for 4 consecutive days beginning within 7 days of onset of fever.151280

In one study, a single 2-g/kg IGIV infusion was at least as effective as a 4-day regimen of 400 mg/kg daily in preventing coronary artery abnormalities,238240 and a single infusion was associated with more rapid defervescence, shorter duration of fever, and more rapid return to normal of clinical measures of inflammation.238240

150–400 mg/kg of IGIV once daily for 5 days or, alternatively, a single dose of 1–2 g/kg has been used.105 Optimal dosage regimen not established.105

Adults

Hepatitis A Virus (HAV) Infection (Preexposure Prophylaxis)

Travelers to Areas with Intermediate or High Levels of Endemic HAV

IM

Single dose of 0.1 or 0.2 mL/kg of IGIM in those staying in such areas for up to 1 or 2 months, respectively.154336 If period of exposure in such areas will be ≥2 months, give 0.2 mL/kg once every 2 months.154336

Primary immunization with the age-appropriate schedule of hepatitis A vaccine before an expected exposure to HAV ensures the highest level of protection.115186187

To ensure protection in travelers who are older adults, immunocompromised, or have chronic liver disease or other chronic medical conditions and plan to depart within 2 weeks, give single dose of IGIM concurrently with first dose of hepatitis A vaccine (using different syringes and different injection sites).115187

The above IGIM dosage is higher than previously recommended.336 This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).336

Hepatitis A Virus (HAV) Infection (Postexposure Prophylaxis)

IM

Adults >40 years of age who have not previously received hepatitis A vaccine: Give single dose of 0.1 mL/kg of IGIM154336 as soon as possible after exposure (ideally within 2 weeks).105186187

Adults ≤40 years of age who have not previously received hepatitis A vaccine: ACIP prefers active immunization with hepatitis A vaccine since it provides long-term protection.187

Immunocompromised individuals, individuals with chronic liver disease, and whenever hepatitis A vaccine is contraindicated: Give single dose of 0.1 mL/kg of IGIM154336 as soon as possible after exposure (ideally within 2 weeks).105186187

In individuals receiving IGIM for HAV postexposure prophylaxis and in whom hepatitis A vaccine also is recommended for other reasons, give IGIM dose concurrently with first dose of hepatitis A vaccine (using different syringes and different injection sites).186187194

Individuals who have received at least 1 dose of hepatitis A vaccine given at least 1 month prior to the current HAV exposure do not need postexposure prophylaxis with IGIM.186

The above IGIM dosage is higher than previously recommended.336 This change was made in 2017 based on data indicating that HAV IgG antibody (anti-HAV IgG) potency of currently available IGIM is lower than in the past (most likely because decreasing prevalence of previous HAV infection among plasma donors resulted in lower anti-HAV antibody levels in donor plasma).336

Measles

Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.25 mL/kg of IGIM given within 6 days after exposure in susceptible individuals.154

ACIP recommends single dose of 0.5 mL/kg (up to 15 mL) of IGIM given within 6 days after exposure.133 ACIP states optimal dose needed to provide protection against measles infection unknown.133

Individuals currently receiving immune globulin replacement therapy who received IGIV (≥400 mg/kg) within 3 weeks prior to measles exposure or immune globulin subcutaneous (≥2 mg/kg) for 2 consecutive weeks prior to measles exposure should be sufficiently protected and do not need IGIM for postexposure prophylaxis.133

IV

Gammaked 10%: If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to expected measles exposure.332 If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.332

Gamunex-C 10%: If patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area), give a dose of at least 400 mg/kg (4 mL/kg) just prior to measles exposure.265 If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg (4 mL/kg) as soon as possible after the exposure.265

Octagam 5%: If a patient is already receiving a dosage <400 mg/kg once every 3–4 weeks and is at risk of measles exposure (i.e., susceptible traveler to measles endemic area, measles outbreak in US), increase dosage to at least 400 mg/kg just prior to measles exposure.263 If a susceptible individual has been exposed to measles, give a dose of 400 mg/kg as soon as possible after the exposure.263

Sub-Q

Hizentra 20%: Use minimum total weekly dose of 200 mg/kg for 2 consecutive weeks in those at risk of measles exposure (e.g., susceptible traveler to measles endemic area, measles outbreak in US).294 If a biweekly sub-Q regimen is being used, give a single dose of at least 400 mg/kg.294 If a susceptible individual has been exposed to measles, give a dose of at least 400 mg/kg as soon as possible after the exposure.294

Rubella

Postexposure Prophylaxis in Pregnant Women

IM

Single dose of 0.55 mL/kg of IGIM.154 Routine use not recommended.105131154

Varicella

Alternative to VZIG for Postexposure Prophylaxis

IM

Manufacturer recommends single dose of 0.6–1.2 mL/kg of IGIM;154 use lower range of dosage in those at risk for thrombosis.154

Single dose of 400 mg/kg of IGIV (ideally within 96 hours after varicella exposure).105156272 Consider IGIV only when VZIG is unavailable.272

May not be necessary in patients already receiving immune globulin replacement therapy with IGIV (≥400 mg/kg given at regular intervals) if the last dose was administered within 3 weeks prior to varicella exposure.105146155156269

Privigen 10%: 200–800 mg/kg (2–8 mL/kg) IV once every 3–4 weeks.292 Adjust dosage over time to achieve desired trough serum IgG concentration and clinical response.292 If a dose is missed, give missed dose as soon as possible and resume scheduled doses once every 3 or 4 weeks as applicable.292

Sub-Q

Cuvitru 20%: Give at regular intervals ranging from once daily up to once every 2 weeks (biweekly).331 Calculate initial sub-Q dose based on monthly dose of prior immune globulin regimen.331 If switching from IGIV or immune globulin subcutaneous 10% with recombinant human hyaluronidase (Hyqvia), give initial dose 1 week after last dose of the other immune globulin.331Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.331

Gammagard Liquid 10%: Administer sub-Q once weekly.266 Give initial dose approximately 1 week after last IGIV dose.266 To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37.266 Base maintenance sub-Q doses on clinical response and target trough IgG concentrations.266Consult manufacturer’s literature for specific information on how to adjust sub-Q dosage based on trough serum IgG concentrations.266

Gammaked 10%: Administer sub-Q once weekly.332 Give initial dose 1 week after last IGIV dose.332 To calculate initial sub-Q weekly dose, divide patient’s previous IGIV dose (in g) by the number of weeks between IGIV doses (i.e., divide by 3 or 4 depending on whether the patient was receiving IGIV every 3 or 4 weeks), then multiply this value by a dose adjustment factor of 1.37.332 Adjust weekly sub-Q dose over time to achieve desired trough serum IgG concentrations and clinical response.332Consult manufacturer’s literature for specific information on how to adjust sub-Q dosage based on trough serum IgG concentrations and for information regarding dosage requirements for patients switching from another immune globulin subcutaneous preparation to Gammaked 10%.332

Hizentra 20%: Administer sub-Q at regular intervals ranging from once daily up to once every 2 weeks (biweekly).294 Use only in patients who have been receiving IGIV for ≥3 months before being switched to Hizentra 20%;294 give initial dose 1 week after last IGIV dose.294Consult manufacturer’s literature for specific information regarding initial and subsequent dosage for sub-Q administration.294

Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Administer sub-Q once every 3 to 4 weeks after an initial ramp-up period that incrementally changes the dosage regimen from a 1-week regimen to a 3- or 4-week regimen and allows the patient to become accustomed to the large volumes required for a full monthly dose.327Consult manufacturer's literature for specific information on the ramp-up schedule, including specific doses and dosing intervals for sub-Q administration.327

Idiopathic Thrombocytopenic Purpura (ITP)

IV

Carimune NF: For induction therapy, usual dosage is 400 mg/kg IV once daily for 2–5 consecutive days.125 If platelet count decreases to <30,000/mm3 and/or clinically important bleeding becomes apparent following initial induction therapy, administer 400 mg/kg as a single maintenance infusion.125 If adequate response does not occur, increase maintenance dose to 800–1000 mg/kg given as a single infusion.125

Gammagard S/D or Gammagard S/D (IgA <1 mcg/mL): Single dose of 1 g/kg IV for chronic ITP.151280 Determine need for additional doses based on clinical response and platelet count.151280 If required, up to 3 doses may be given on alternate days.151280

Gammaked 10%: 1 g/kg (10 mL/kg) IV once daily for 2 consecutive days (total dose 2 g/kg);332 if increase in platelet count adequate 24 hours after first dose, second dose may be withheld.332 Alternatively, give 400 mg/kg (4 mL/kg) once daily for 5 consecutive days (total dose 2 g/kg).332 High-dose regimen (1 g/kg for 1 or 2 doses) not recommended in patients with expanded fluid volumes or when fluid volume may be a concern.332

Individuals with B-cell Chronic Lymphocytic Leukemia (CLL)

Hypogammaglobulinemia and/or Recurrent Bacterial Infections

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

IV

Gammaked 10%: Loading dose of 2 g/kg (20 mL/kg) given in divided doses over 2–4 consecutive days.332 Then, maintenance dosage of 1 g/kg (10 mL/kg) given as a single dose once every 3 weeks or, alternatively, 2 doses of 0.5 g/kg (5 mL/kg) given on 2 consecutive days once every 3 weeks.332

Gamunex-C 10%: Loading dose of 2 g/kg (20 mL/kg) given in divided doses over 2–4 consecutive days.265 Then, maintenance dosage of 1 g/kg (10 mL/kg) given as a single dose once every 3 weeks or, alternatively, 2 doses of 0.5 g/kg (5 mL/kg) given on 2 consecutive days once every 3 weeks.265 Has been continued for up to 48 weeks in clinical studies in patients with CIDP.298

Multifocal Motor Neuropathy (MMN)

IV

Although optimum dosage not established, if IGIV used when disability is severe enough to warrant treatment, the European Federation of Neurological Societies (EFNS) and Peripheral Nerve Society (PNS) suggest an initial IGIV dosage of 2 g/kg given in divided doses over 2–5 consecutive days.310311 If initial regimen is effective, these clinicians state that maintenance therapy can be considered using 1 g/kg once every 2–4 weeks or 2 g/kg every 1–2 months;310311 frequency of maintenance therapy should be guided by response.310311

IV

Although safety and efficacy and optimum dosage not established,312317318 EFNS and others recommend 0.4 g/kg of IGIV daily for 5 days.301310312 Unclear whether IGIV is effective when initiated more than 2 weeks after symptom onset.317

If relapse occurs after an initial response, EFNS states that retreatment with a dosage of 2 g/kg of IGIV given in divided doses over 2–5 consecutive days can be considered.310 Retreatment also can be considered in those who do not respond to initial regimen,310 but other clinicians state it is unclear whether retreatment is beneficial in such patients.305318

Adults

Measles

Postexposure Prophylaxis

Special Populations

Hepatic Impairment

Renal Impairment

Reduce IGIV dose, concentration, and/or rate of administration; maximum safe dose, concentration, and rate of administration not established.125151249263265266282 Ensure that patients are not volume depleted and are well hydrated; administer at the minimum concentration available and minimum practicable rate of infusion.125151249263265266280282292308324325326332 (See Renal Effects under Cautions and see IV Administration under Dosage and Administration.)

Geriatric Patients

Reduce IGIV dose, concentration, and/or rate of infusion in patients >65 years of age; maximum safe dose, concentration, and rate of administration not established.125151249280263265266282 Administer IGIV and immune globulin subcutaneous at minimum practicable rate of infusion.125151249263265266280282292294308324325326331332 (See Renal Effects under Cautions and see IV Administration under Dosage and Administration.)

Because of potential increased risk of thrombosis, consider baseline assessment of blood viscosity in patients at risk for hyperviscosity (e.g., those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], or monoclonal gammopathies).125151263265266282292294308324325326327328329331332

Renal Effects

Patients at increased risk for acute renal failure include, but are not limited to, those with any degree of preexisting renal insufficiency, diabetes mellitus, volume depletion, sepsis, or paraproteinemia; those receiving concomitant nephrotoxic drugs; and/or those >65 years of age.125151249263265266282308327

IGIV preparations stabilized with sucrose (e.g., Carimune NF) have been associated with renal dysfunction more frequently than other IGIV preparations;125249263265266282308 weigh benefits of these preparations against potential risk of renal dysfunction.249 Maximum infusion rate of 3 mg of sucrose/kg per minute recommended.125249261

To reduce risk of acute renal failure, ensure that patients are not volume depleted and are adequately hydrated prior to administration of IGIV or immune globulin subcutaneous and use lowest effective dosage.125249251265266282292294308324325326327

Administer IGIV or immune globulin subcutaneous at the minimum concentration available and the minimum infusion rate practicable, especially in patients at increased risk for acute renal failure.125151249263265266282294308

Assess urine output and renal function (BUN, Scr) prior to and at appropriate intervals during therapy with IGIV or immune globulin subcutaneous, especially in patients considered at increased risk for acute renal failure.125151249263265266282292294308324325326327331332

Infusion Reactions

Increased risk of infusion reactions (e.g., fever, chills, nausea, vomiting) when immune globulin administered by IV or sub-Q infusion in patients who have not previously received immune globulin therapy, in patients being switched to a different immune globulin preparation, and in those who have not received immune globulin within the preceding 8 weeks.125265266282325

IGIV may cause a precipitous fall in BP and clinical manifestations of anaphylaxis, which appear to be related to the rate of IGIV infusion; do not exceed the recommended rate of infusion.265266282 These reactions generally appear 0.5–1 hour after initiation of the infusion and include facial flushing, chest tightness, chills, fever, dizziness, nausea, vomiting, diaphoresis, and hypotension or hypertension.125 Closely monitor for adverse reactions throughout the infusion125282292 since these reactions may rarely lead to shock.125282

If flushing, changes in BP or pulse, or other infusion reactions occur, slow or temporarily stop the infusion.125266 In some cases when symptoms subside promptly, the infusion may be resumed at a rate that is comfortable for the patient.125266292 Stop infusion immediately if anaphylaxis or other severe reactions occur.125 (See Sensitivity Reactions under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Epinephrine and antihistamines should be readily available in case anaphylaxis or an anaphylactoid reaction occurs.125151263265266282292308 If a severe hypersensitivity reaction occurs, discontinue immune globulin immediately and institute appropriate therapy as indicated.154263265292294308324325326327

Use IGIM with caution in patients with a history of systemic allergic reactions to immune globulin preparations.154

The manufacturer of IGIM states that intradermal sensitivity testing should not be performed;154 intradermal injection of concentrated buffered immune globulin solution frequently causes localized chemical irritation, which may be misinterpreted as evidence of hypersensitivity and result in needed therapy being withheld.154

Individuals with selective IgA deficiency or individuals in whom IgA deficiency exists as a component of an immunodeficiency disease may have serum antibodies to IgA or may develop such antibodies following administration of immune globulin or other blood products containing IgA.125151154263265266280282292294 Potential for severe hypersensitivity (e.g., anaphylactic) reactions to IgA in such patients.125151154263265266280282292294308327

Administer only in a setting where supportive care is available for treating life-threatening reactions.266282 If a hypersensitivity reaction occurs, consider alternative therapy.266280

All commercially available preparations of IGIV contain trace amounts of IgA, but the amount varies among the different preparations.262263265266280292 There is some evidence that IGIV preparations depleted of IgA (0.4–2.9 mcg/mL of IgA) may be better tolerated in patients who react to IGIV preparations containing higher IgA concentrations.151 However, concentration of IgA that will not provoke a reaction to IgA not known.151280 All IGIV preparations carry the risk of inducing an anaphylactic reaction to IgA;151280 risk of anaphylaxis may exist despite use of preparations containing only trace amounts of IgA.151

Corn Allergy

Octagam 5% and Octagam 10% contain maltose, a disaccharide sugar derived from corn.263326 Hypersensitivity reactions may occur if these preparations are used in patients with corn allergy.263326 Manufacturer states avoid Octagam 5% in patients with known corn allergies;263 contraindicated in those with acute hypersensitivity reactions to corn.263

Other Warnings and Precautions

Hemolysis

IGIV and immune globulin subcutaneous may contain blood group antibodies that can act as hemolysins and induce in vivo coating of RBCs with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis.125151263265266282292294308324325326327

Monitor for clinical signs and symptoms of hemolysis (e.g., increased heart rate, swelling, fatigue, difficulty breathing, yellowing of skin or eyes, dark-colored urine) and, if necessary, perform confirmatory laboratory testing.125151263265266282292294308324325326327 If a blood transfusion is indicated for a patient who developed hemolysis with clinically compromising anemia after receiving immune globulin, adequate cross-matching should be performed to avoid exacerbating on-going hemolysis.292294308

In patients exhibiting such symptoms, perform a thorough neurologic examination, including CSF studies, to rule out other causes of meningitis.125151263265266282294308324332 CSF analysis frequently reveals elevated protein levels (up to several hundred mg/dL) and pleocytosis (up to several thousand cells per mm3), predominantly from the granulocytic series,125151211212263265266282294308324332 but negative culture results.265266292324332

Hyperproteinemia, Increased Viscosity, and Hyponatremia

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV.263265280282292308324325326 The hyponatremia is likely to be pseudohyponatremia, as demonstrated by decreased calculated serum osmolality or elevated osmolar gap.263265266292308325

If hyponatremia occurs, it is critical to distinguish true hyponatremia from pseudohyponatremia.263265266292308324325326332 Treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and may predispose to thromboembolic events.263265266292308324332 (See Thrombosis under Cautions.)

Gammagard S/D and Gammagard S/D (IgA <1 mcg/mL) contain approximately 8.5 mg of sodium chloride per mL;151280 consider this amount when determining dietary sodium in patients on a low-sodium diet since hypernatremia may occur.151280

Volume Overload

Because of risk of volume overload, manufacturers of Gammaplex 5% and Privigen 10% state carefully consider relative risks and benefits before using high-dose IGIV regimens (1 g/kg daily for 1–2 days) for treatment of chronic ITP in patients at increased risk of volume overload.292308

Manufacturers of Gammaked 10% and Gamunex-C 10% state high-dose IGIV regimens (1 g/kg daily for 1–2 days) not recommended for treatment of chronic ITP in individuals with expanded fluid volumes or when fluid volume may be a concern.265332

Risk of Transmissible Agents in Plasma-derived Preparations

Because immune globulin preparations are prepared from pooled human plasma, they may carry a risk of transmitting human viruses (e.g., HAV, HBV, HCV, HIV) and theoretically may carry a risk of transmitting the causative agents of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).125151154210263265266282292294308324325326

Risk for transmission of recognized blood-borne viruses is considered to be low because plasma donors are screened for certain viruses (HBV, HCV, HIV) and viral reduction/inactivation procedures used in immune globulin production reduce the risk of transmission.151154263265266282292294308324325326327 Despite such stringent procedures, a risk of transmission still remains.125151154227263265266282292324325326

Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge that may not be inactivated by the manufacturing processes or various treatment procedures used, carefully weigh risk of pathogen transmission against the benefits of immune globulin therapy.125151154227263265266292

Animal studies indicate that antibodies to recombinant human hyaluronidase cross the placenta and are transferred to offspring during lactation.327 These antibodies could potentially cross-react with endogenous human hyaluronidase (expressed in adult male testes, epididymis, and sperm).327

Individuals with Bleeding Disorders

Bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy.134 Manufacturer states that IGIM should not be used in individuals with severe thrombocytopenia or any coagulation disorder that would contraindicate IM injections.154

ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient’s bleeding risk determines that the preparation can be administered with reasonable safety.134 In these cases, use a fine needle (23 gauge or smaller) and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.134 If patient is receiving antihemophilia therapy, administer the IM dose shortly after a scheduled dose of such therapy.134

Lactation

Not known whether immune globulin is distributed into milk following IM, IV, or sub-Q administration;266281325326 use with caution in nursing women.266326

Hyqvia (immune globulin subcutaneous 10% with recombinant human hyaluronidase): Use in nursing women only if clearly needed.327 Animal studies indicate maternal antibodies bound to recombinant human hyaluronidase are transferred to offspring during lactation.327 Possible effects of antibodies to recombinant human hyaluronidase that may be transferred to infants unknown.327

Pediatric Use

GamaSTAN S/D: Manufacturer states safety and efficacy of IGIM not established in pediatric patients;154 however, passive immunization with IGIM is recommended by ACIP, AAP, and CDC in pediatric patients under certain circumstances.105115133186187231 (See Hepatitis A Virus [HAV]) Infection [Preexposure Prophylaxis], Hepatitis A Virus [HAV] Infection [Postexposure Prophylaxis], and Measles, under Uses.)

Bivigam 10%: Safety and efficacy not established in children <6 years of age.324 Only limited data regarding efficacy and safety in pediatric patients.324

Carimune NF: Studies using high doses in pediatric patients with acute or chronic ITP did not reveal any specific differences in safety in pediatric patients versus adults.125

Cuvitru 20%: Safety and efficacy not established in pediatric patients <2 years of age.331

Flebogamma 5% DIF: Safety and efficacy not established in pediatric patients <2 years of age.282

Flebogamma 10% DIF: Safety and efficacy not established for treatment of primary immunodeficiency in pediatric patients.325 Evaluated in a limited number of children and adolescents with chronic ITP;325 safety and efficacy not established for treatment of chronic ITP in children <2 years of age.325

Gammagard Liquid 10%: Safety and efficacy for treatment of primary immunodeficiency not established in children <2 years of age.266 Safety and efficacy for treatment of MMN not established in pediatric patients of any age.266

Gammagard S/D and Gammagard S/D (IgA <1 mcg/mL): Clinical studies in patients with primary immunodeficiency did not include sufficient numbers of pediatric patients ≤16 years of age to determine whether they respond differently than adults.151280 Safety and efficacy not established for treatment of ITP in pediatric patients.151280 Safety and efficacy established for treatment of Kawasaki disease in pediatric patients;151280 majority of patients in clinical studies were <5 years of age.151280

Gammaked 10%: Safety and efficacy of IV route established for treatment of primary immunodeficiency in pediatric patients;332 safety and efficacy of sub-Q route not established for treatment of primary immunodeficiency in pediatric patients <2 years of age.332 Safety and efficacy of IV (not sub-Q) route established for treatment of ITP in pediatric patients.332 Safety and efficacy not established for treatment of CIDP in pediatric patients.332

Gammaplex 5%: Safety and efficacy for treatment of primary immunodeficiency not established in children <2 years of age.308 Clinical studies in patients with ITP included only limited number of children;308 data insufficient to determine whether efficacy in pediatric patients with ITP differs from that in adults.308

Gamunex-C 10%: Safety and efficacy of IV route established for treatment of primary immunodeficiency in pediatric patients;265 safety and efficacy of sub-Q route not established for treatment of primary immunodeficiency in pediatric patients <2 years of age.265 Safety and efficacy of IV (not sub-Q) route established for treatment of ITP in pediatric patients.265 Safety and efficacy not established for treatment of CIDP in pediatric patients.265

Hizentra 20%: Safety and efficacy not established in pediatric patients <2 years of age.294 Safety and efficacy established for sub-Q replacement therapy in pediatric patients 2–16 years of age with primary immunodeficiency.294 No differences in safety and efficacy profiles in pediatric patients compared with adults;294 pediatric-specific dosage not required to achieve desired serum IgG concentrations.294

Octagam 5%: Evaluated in a limited number of children 6–16 years of age;263 no apparent differences in pharmacokinetics, efficacy, or safety compared with adults.263 Pediatric-specific dosage not required to achieve desired serum IgG concentrations.263

Octagam 10%: Safety and efficacy not established in pediatric patients.326

Privigen 10%: Safety and efficacy for treatment of primary immunodeficiency not established in pediatric patients <3 years of age.292 Has been evaluated in a limited number of children and adolescents with primary immunodeficiency;292 no apparent differences in safety and efficacy compared with adults.292 Pediatric-specific dosage not required to achieve desired serum IgG concentrations.292 Safety and efficacy not established for treatment of chronic ITP in pediatric patients <15 years of age.292

Geriatric Use

IGIV: Clinical studies of IGIV did not include a sufficient number of patients ≥65 years of age to determine whether geriatric individuals respond differently than younger patients.263265266292308324325326 Use with caution;125265292308324 do not exceed recommended dosage;125265266292 administer at the minimum concentration available and minimum practicable infusion rate.125151263265266282292308324325326 (See Renal Effects under Cautions and see Geriatric Patients under Dosage and Administration.)

Immune globulin subcutaneous: Only limited number of patients ≥65 years of age were included in clinical studies of Cuvitru 20%, Gammagard Liquid 10%, Hizentra 20%, or Hyqvia;266294327331 no overall differences in safety or efficacy were observed compared with younger patients.266294331

Renal Impairment

Patients receiving IGIV who have any degree of preexisting renal insufficiency are at increased risk for acute renal failure.125151249263265266282292308324325326332 Ensure that such patients are not volume depleted and are well hydrated and administer IGIV at the minimum concentration available and minimum practicable rate of infusion.125151249263265266282292308324325326332 (See Renal Effects under Cautions and see Renal Impairment under Dosage and Administration.)

Interactions for Immune Globulin

Live Vaccines

Antibodies present in immune globulin preparations may interfere with immune response to some live virus vaccines, including MMR and varicella virus vaccine live;105125134185263265292294308324325326327331332 no evidence of interference with immune responses to influenza virus vaccine live intranasal, yellow fever virus vaccine live, typhoid vaccine live oral, rotavirus vaccine live oral, zoster vaccine live, or poliovirus vaccine live oral (OPV; no longer commercially available in US).105134185 (See Specific Drugs and Laboratory Tests under Interactions.)

Inactivated Vaccines and Toxoids

ACIP and AAP state that administration of inactivated vaccines and toxoids simultaneously with (at different sites) or at any interval before or after administration of immune globulin preparations should not have clinically important effects on immune responses to the vaccines or toxoids.105134

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Hepatitis A virus vaccine inactivated

Anti-HAV antibody passively acquired from immune globulin may decrease active immune response stimulated by the vaccine, but seroconversion rates are not affected105186195197208

May administer simultaneously at separate sites using different syringes105186194195208289

Influenza virus vaccine live intranasal

No evidence that immune globulin preparations interfere with immune response to the vaccine105134185

Vaccine may be given simultaneously with or at any interval before or after immune globulin105134185

Measles, mumps, rubella, and varicella virus vaccines

Antibodies in immune globulin can interfere with immune responses to measles and rubella antigens contained in MMR or MMRV;105125131134154185263266294308 effect on immune responses to mumps or varicella antigens unknown105134

Duration of interference depends on amount of antigen-specific antibody in the immune globulin preparation134185

MMR, MMRV, or varicella vaccine: Do not administer simultaneously with or for specified intervals before or after administration of immune globulin105125134185263265

ACIP and AAP recommend deferring administration of MMR, MMRV, or varicella vaccine for 3 months following IGIM for preexposure or postexposure HAV prophylaxis;105134154185186 for 5 months following IGIM for measles prophylaxis in immunocompetent individuals;105134185 for 6 months following IGIM for measles prophylaxis in immunodeficient individuals;105134185 for 8 months following IGIV for replacement therapy of immunodeficiencies105134185 or for postexposure varicella prophylaxis;269 for 8–10 months following IGIV for treatment of ITP;105134185 and for 11 months following IGIV for Kawasaki disease105134185

If MMR, MMRV, or varicella vaccine is administered simultaneously (at a separate site) or at a shorter-than-recommended interval, ACIP and AAP recommend administration of an additional vaccine dose at the recommended interval after the immune globulin dose, unless serologic testing is feasible and indicates an adequate antibody response to the vaccine134185

Poliovirus vaccine live oral (OPV; no longer commercially available in US)

No evidence that immune globulin preparations interfere with immune response to the vaccine105185186

May be given simultaneously with or at any interval before or after immune globulin105185

Rotavirus vaccine

Potential for decreased antibody response to rotavirus vaccine in infants who recently received immune globulin;296309 safety and efficacy data not available regarding use of rotavirus vaccine in infants who have received immune globulin within the last 42 days295296

ACIP and AAP state rotavirus vaccine may be administered simultaneously with or at any time before or after antibody-containing blood products105134296309

Possible false-positive tests for diagnosis of fungal infection when assay depends on detection of beta-d-glucans;151266280331 test interference may persist during the weeks following infusion of immune globulin151266280331

Stability

Storage

Parenteral

Injection for IM Use

Injection for IV Infusion

Bivigam 10%: 2–8°C.324 Do not freeze or heat;324 discard if frozen or heated.324 Promptly use vials that have been entered.324 Discard partially used vials.324

Flebogamma 5% DIF: 2–25°C;282 stable for up to 24 months as indicated by expiration date on outer carton and container label.282 Do not freeze;282 discard if frozen.282 Discard partially used vials.282 Protect from light by storing in original carton.282

Flebogamma 10% DIF: 2–25°C;325 stable for up to 24 months as indicated by expiration date on outer carton and container label.325 Do not freeze;325 discard if frozen.325 Discard partially used vials.325 Protect from light by storing in original carton.325

Gammaplex 5%: 2–25°C for up to 36 months after date of manufacture.308 Do not freeze;308 discard if frozen.308 Protect from light by storing in original carton.308 Promptly use bottles that have been entered;308 discard partially used bottles.308

Octagam 5%: 2–25°C for 24 months after date of manufacture.263 Do not freeze;263 discard if frozen.263 Promptly use bottles that have been entered;263 discard partially used bottles.263

Octagam 10%: 2–8°C for 24 months after date of manufacture.326 Alternatively, may be stored at room temperature (≤25°C) for up to 9 months at any time during first 12 months from date of manufacture, but then must be used immediately or discarded.326 Do not freeze;326 discard if frozen.326 Promptly use bottles that have been entered;326 discard partially used bottles.326

Privigen 10%: Room temperature (≤25ºC) for up to 36 months after date of manufacture as indicated by expiration date on outer carton and vial label.292 Do not freeze;292 discard if frozen.292 Protect from light.292

Powder for Injection, for IV Infusion

Carimune NF: Room temperature (≤30°C);125 may be stored until expiration date indicated on vial label.125 Use promptly if reconstituted outside of sterile laminar airflow conditions;125 use within 24 hours if reconstituted in a sterile laminar flow hood using aseptic technique and stored under refrigeration.125 Do not freeze reconstituted solution.125 Discard partially used vials.125

Gammagard S/D and Gammagard S/D (IgA <1 mcg/mL): ≤25°C;151280 do not freeze.151280 If reconstituted outside of sterile laminar airflow conditions, use within 2 hours; if reconstituted in a sterile laminar flow hood using aseptic technique, may be stored at 2–8°C for up to 24 hours.151280 Discard partially used vials.151280

Injection for Sub-Q Infusion

Cuvitru 20%: 2–8°C for up to 36 months.331 Alternatively, store at room temperature (≤25°C) for up to 12 months;331 do not return to refrigeration.331 Do not freeze.331 To protect from light, store in original carton until used.331 Discard partially used vials.331

Hizentra 20%: Room temperature (≤25°C) for up to 30 months as indicated by expiration date on outer carton and vial label.294 Do not freeze;294 discard if frozen.294 To protect from light, store in original carton until used.294 Discard partially used vials.294

Hyqvia (kit containing immune globulin subcutaneous 10% with recombinant human hyaluronidase): 2–8°C for up to 36 months as indicated by expiration date on outer carton and vial label.327 Alternatively, may be stored for up to 3 months at room temperature (≤25°C) during first 24 months from date of manufacture;327 do not return to refrigeration.327 Do not freeze.327 To protect from light, store in original carton until used.327 Discard partially used vials.327

Injection for IV or Sub-Q Infusion

Gammagard Liquid 10%: 2–8°C for ≤36 months as indicated by expiration date on outer carton and container label.266 Alternatively, may be stored at ≤25°C for up to 24 months as indicated by expiration date on outer carton and container label.266 Do not freeze.266 Vials are for single use only.266 Discard partially used vials.266

Gammaked 10%: 2–8°C for 36 months after date of manufacture.332 May be stored at room temperature (≤25°C) for up to 6 months at any time during the 36 months, but then must be used immediately or discarded.332 Do not freeze;332 discard if frozen.332 Promptly use vials that have been entered;332 discard partially used vials.332

Gamunex-C 10%: 2–8°C for 36 months after date of manufacture.265 May be stored at room temperature (≤25°C) for up to 6 months at any time during the 36 months, but then must be used immediately or discarded.265 Do not freeze.265 Promptly use vials that have been entered;265 discard partially used vials.265

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Mechanism of action in the treatment of primary humoral immunodeficiency not fully elucidated.263265292294308

Mechanism by which IGIV increases platelet counts in the treatment of ITP not fully elucidated.125130139140142265292 May saturate Fc (crystallizable fragment) receptors on cells of the reticuloendothelial system, resulting in decreased Fc-mediated phagocytosis of antibody-coated cells.130139142 Altered Fc-receptor affinity for IgG or suppression of antiplatelet antibody production may be involved.139140142

Mechanism by which IGIV reduces the incidence of acute GVHD following BMT not determined.221

Mechanism of action of IGIV in the treatment of chronic inflammatory demyelinating polyneuropathy not fully elucidated.265

Mechanism of action of IGIV in the treatment of Kawasaki disease is not known,299 but possibly may include modulation of cytokine production, neutralization of bacterial superantigens or other etiologic agents, augmentation of T-cell suppressor activity, suppression of antibody synthesis, and provision of anti-idiotypic antibodies.299 IGIV and aspirin appear to have additive anti-inflammatory effects in the treatment of Kawasaki disease.299

Carimune NF: Following reconstitution, contains 30–120 mg of protein per mL.125 Contains ≥96% IgG; most of the immunoglobulins are monomeric (7S) IgG; the remainder are dimeric IgG, small amounts of polymeric IgG, traces of IgA and IgM, and immunoglobulin fragments.125 Distribution of IgG subclasses corresponds to that of normal serum.125

Cuvitru 20%: Contains 20% protein, of which ≥98% is IgG.331 Distribution of IgG subclasses is similar to that of normal plasma.331 Fc and Fab functions are maintained.331

Gammagard Liquid 10%: Contains ≥98% IgG, IgA (average 37 mcg/mL), and trace amounts of IgM.266 Distribution of IgG subclasses is similar to that of normal serum.266 Fc and Fab functions are maintained.266

Gammagard S/D: Following reconstitution, contains approximately 50 mg of protein per mL.151 Contains ≥90% IgG and trace amounts of IgA (<1 mcg/mL or ≤2.2 mcg/mL, depending on the formulation) and IgM.151280 Distribution of IgG subclasses is similar to that of normal serum.151 Fc portion is maintained intact.280

Gammaked 10%: Contains 9–11% protein stabilized in 0.16–0.24 M glycine;332 ≥98% of protein content has the electrophoretic mobility of IgG.332 Distribution of IgG subclasses is similar to that of normal serum;332 contains trace amounts of fragments, IgA (average 46 mcg/mL), and IgM.332

Gamunex-C 10%: Contains 9–11% protein;265 ≥98% of the protein content has the electrophoretic mobility of IgG.265 Contains trace amounts of fragments, IgA (average 46 mcg/mL), and IgM.265 Distribution of IgG subclasses is similar to that of normal serum.265 Fc and Fab functions are maintained, but do not activate complement or pre-Kallikrein activity in unspecific manner.265

Hizentra 20%: Contains 200 mg of protein per mL, of which ≥98% is IgG.294 The Fc and Fab functions of the IgG molecule are retained.294 Contains trace amounts of IgA (≤50 mcg/mL).294 Also contains approximately 250 mmol/L (range 210–290 mmol/L) of l-proline (a nonessential amino acid) as a stabilizer, polysorbate 80 (8–30 mg/L), and trace amounts of sodium.294

If the patient and/or caregiver are considered competent to safely administer immune globulin subcutaneous in the home or other appropriate setting, ensure that they receive instructions and training regarding proper dosage and administration.265266294326327331332

Advise patients of the importance of immediately informing a clinician if symptoms of thrombosis occur, including pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, unexplained rapid pulse, chest pain or discomfort that worsens on deep breathing, numbness or weakness on one side of the body, changes in mental status/confusion, numbness in the face or extremities, weakness or paralysis, severe headache, and/or visual disturbances.125151154263265266282294308324325326327328331332

Importance of immediately informing clinician if increased heart rate, fatigue, yellowing of skin or eyes, or dark-colored urine occurs since these are possible signs and symptoms of hemolytic anemia.263265292294308327332

Advise patients that immune globulin is prepared from pooled human plasma.263265266292294308324325326327332 Although improved donor screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, a risk of transmission of human viruses or other pathogens still remains.125151154227263265266294308324325326327332 Importance of reporting any infection believed to have been transmitted by the immune globulin preparation.125151263265266282292308332

Advise patients with selective IgA deficiency that IGIV, IGIM, and immune globulin subcutaneous contain trace amounts of IgA and potentially could result in life-threatening allergic reactions if used in patients who have developed antibodies to IgA.154265266280282292324325326327331

Advise patients receiving Octagam that this preparation contains maltose and may cause falsely-elevated glucose readings when blood glucose monitoring systems based on GDH-PQQ are used; this could result in inappropriate administration of insulin and life-threatening hypoglycemia or could mask true hypoglycemia.263267 Importance of using glucose-specific test methods not affected by maltose.263267

115. Centers for Disease Control and Prevention. CDC health information for international travel, 2018. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website. http://wwwnc.cdc.gov/travel/page/yellowbook-home

131. Centers for Disease Control and Prevention. Control and prevention of rubella: evaluation and management of suspected outbreaks, rubella in pregnant women, and surveillance for congenital rubella syndrome. MMWR Recomm Rep. 2001; 50(RR-12):1-23. http://www.cdc.gov/mmwr/PDF/rr/rr5012.pdf

155. Panel on Opportunistic Infections in HIV-infected Adults and Adolescents. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Accessed October 23, 2015. Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

156. Panel on Opportunistic Infections in HIV-exposed and HIV-infected children, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics (December 15, 2016). Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

187. Centers for Disease Control and Prevention. Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007; 56:1080-4. http://www.ncbi.nlm.nih.gov/pubmed/17947967?dopt=AbstractPlus

210. US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) by blood and blood products. May 2010; updated January 2016. From FDA website. https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM307137.pdf